Depakote

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For Patients

Depakote (divalproex sodium) is a stable co-ordination compound comprised of sodium valproate and valproic acid used to treat manic episodes associated with bipolar disorder, epilepsy, and migraine headaches. Generic Depakote (termed divalproex sodium) is available under several other names. Side effects of Depakote include GI symptoms of nausea, vomiting, diarrhea and constipation, mood swings, agitation, abnormal body movements, and hair loss.

Depakote tablets are available in strengths of 125, 250 and 500 mg tablets. The dose depends on the problem being treated, the age of the patient, and the patient's response to the medication. In general, the maximum recommended dosage is 60 mg/kg/day; some doctors may use lab tests to determine peak and trough (low) level of the drug. Severe side effects of Depakote include liver toxicity and pancreatitis. Other potentially severe side effects include unusual bruising or bleeding, blisters, severe rash, confusion, difficulty swallowing or breathing, joint weakness, depression, and suicidal ideation. Depakote interacts with other drugs (for example, carbapenem antibiotics) that may decrease its levels; it may react with other drugs so the doctor will need a list of drugs the patient is taking. Depakote has been used in children under 2 yrs of age, but they have a high incidence of liver problems. Use of Depakote is not recommended in pregnancy; there is clear evidence of risk to the human fetus, but the benefits may outweigh the risk for pregnant women who have a serious condition that cannot be treated effectively with a safer drug. However, many doctors suggest there is little risk to the infant even though the drug can be detected in breast milk, although they suggest the infant be monitored for any effects.

Our Depakote Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Seek emergency medical attention if the person taking this medicine has nausea, vomiting, upper stomach pain, or loss of appetite, low fever, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes). These symptoms may be early signs of liver damage or pancreatitis.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, depression, anxiety, or if you feel agitated, hostile, restless, hyperactive (mentally or physically), or have thoughts about suicide or hurting yourself.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these other serious side effects:

unexplained weakness with vomiting and confusion or fainting;

easy bruising or bleeding, blood in your urine;

fever, chills, body aches, swollen glands, flu symptoms;

urinating less than usual;

extreme drowsiness, lack of coordination, hallucinations;

double vision or back-and-forth movements of the eyes; or

severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Less serious side effects may include:

mild drowsiness or weakness;

diarrhea, constipation, upset stomach;

changes in your menstrual periods;

enlarged breasts, weight changes;

tremor (shaking);

hair loss;

vision changes; or

unusual or unpleasant taste in your mouth.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

You may rarely see partial tablets in your stool. This may occur if you have certain intestinal disorders (such as ileostomy, colostomy). Tell your doctor right away if you see partial tablets in your stool.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these serious side effects occur: signs of infection (e.g., fever, persistent sore throat).

A small number of people who take anticonvulsants for any condition (such as seizure, bipolar disorder, pain) may experience depression, suicidal thoughts/attempts, or other mental/mood problems. Tell your doctor immediately if you or your family/caregiver notice any unusual/sudden changes in your mood, thoughts, or behavior including signs of depression, suicidal thoughts/attempts, thoughts about harming yourself.

A serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

SIDE EFFECTS

Because clinical studies are conducted under widely
varying conditions, adverse reaction rates observed in the clinical studies of
a drug cannot be directly compared to rates in the clinical studies of another
drug and may not reflect the rates observed in practice.

Mania

The incidence of treatment-emergent events has been
ascertained based on combined data from two three week placebo-controlled
clinical trials of Depakote in the treatment of manic episodes associated with
bipolar disorder. The adverse reactions were usually mild or moderate in
intensity, but sometimes were serious enough to interrupt treatment. In
clinical trials, the rates of premature termination due to intolerance were not
statistically different between placebo, Depakote, and lithium carbonate. A
total of 4%, 8% and 11% of patients discontinued therapy due to intolerance in
the placebo, Depakote, and lithium carbonate groups, respectively.

Table 2 summarizes those adverse reactions reported for
patients in these trials where the incidence rate in the Depakote-treated group
was greater than 5% and greater than the placebo incidence, or where the
incidence in the Depakote-treated group was statistically significantly greater
than the placebo group. Vomiting was the only reaction that was reported by
significantly (p ≤ 0.05) more patients receiving Depakote compared to
placebo.

Epilepsy

Based on a placebo-controlled trial of adjunctive therapy
for treatment of complex partial seizures, Depakote was generally well
tolerated with most adverse reactions rated as mild to moderate in severity.
Intolerance was the primary reason for discontinuation in the Depakotetreated
patients (6%), compared to 1% of placebo-treated patients.

Table 3 lists treatment-emergent adverse reactions which
were reported by ≥ 5% of Depakotetreated patients and for which the
incidence was greater than in the placebo group, in the placebo-controlled
trial of adjunctive therapy for treatment of complex partial seizures. Since
patients were also treated with other antiepilepsy drugs, it is not possible,
in most cases, to determine whether the following adverse reactions can be
ascribed to Depakote alone, or the combination of Depakote and other
antiepilepsy drugs.

Table 4 lists treatment-emergent adverse reactions which were reported by ≥ 5% of
patients in the high dose valproate group, and for which the incidence was
greater than in the low dose group, in a controlled trial of Depakote
monotherapy treatment of complex partial seizures. Since patients were being
titrated off another antiepilepsy drug during the first portion of the trial,
it is not possible, in many cases, to determine whether the following adverse
reactions can be ascribed to Depakote alone, or the combination of valproate
and other antiepilepsy drugs.

Table 4: Adverse Reactions
Reported by ≥ 5% of Patients in the High Dose Group in the Controlled
Trial of Valproate Monotherapy for Complex Partial Seizures1

Body System/Reaction

High Dose (%)
(n = 131)

Low Dose (%)
(n = 134)

Body as a Whole

Asthenia

21

10

Digestive System

Nausea

34

26

Diarrhea

23

19

Vomiting

23

15

Abdominal Pain

12

9

Anorexia

11

4

Dyspepsia

11

10

Hemic/Lymphatic System

Thrombocytopenia

24

1

Ecchymosis

5

4

Metabolic/Nutritional

Weight Gain

9

4

Peripheral Edema

8

3

Nervous System

Tremor

57

19

Somnolence

30

18

Dizziness

18

13

Insomnia

15

9

Nervousness

11

7

Amnesia

7

4

Nystagmus

7

1

Depression

5

4

Respiratory System

Infection

20

13

Pharyngitis

8

2

Dyspnea

5

1

Skin and Appendages

Alopecia

24

13

Special Senses

Amblyopia/Blurred Vision

8

4

Tinnitus

7

1

1 Headache was the only adverse reaction that
occurred in ≥ 5% of patients in the high dose group and at an equal or
greater incidence in the low dose group.

The following additional
adverse reactions were reported by greater than 1% but less than 5% of the 358
patients treated with valproate in the controlled trials of complex partial
seizures:

Migraine

Based on two placebo-controlled clinical trials and their
long term extension, valproate was generally well tolerated with most adverse
reactions rated as mild to moderate in severity. Of the 202 patients exposed to
valproate in the placebo-controlled trials, 17% discontinued for intolerance.
This is compared to a rate of 5% for the 81 placebo patients. Including the
long term extension study, the adverse reactions reported as the primary reason
for discontinuation by ≥ 1% of 248 valproate-treated patients were
alopecia (6%), nausea and/or vomiting (5%), weight gain (2%), tremor (2%),
somnolence (1%), elevated SGOT and/or SGPT (1%), and depression (1%).

Table 5 includes those adverse reactions reported for
patients in the placebo-controlled trials where the incidence rate in the
Depakote-treated group was greater than 5% and was greater than that for
placebo patients.

Other Patient Populations

Adverse reactions that have been reported with all dosage
forms of valproate from epilepsy trials, spontaneous reports, and other sources
are listed below by body system.

Gastrointestinal

The most commonly reported side effects at the initiation
of therapy are nausea, vomiting, and indigestion. These effects are usually
transient and rarely require discontinuation of therapy. Diarrhea, abdominal
cramps, and constipation have been reported. Both anorexia with some weight
loss and increased appetite with weight gain have also been reported. The
administration of delayed-release divalproex sodium may result in reduction of
gastrointestinal side effects in some patients.

CNS Effects

Sedative effects have occurred in patients receiving
valproate alone but occur most often in patients receiving combination therapy.
Sedation usually abates upon reduction of other antiepileptic medication.
Tremor (may be dose-related), hallucinations, ataxia, headache, nystagmus,
diplopia, asterixis, “spots before eyes”, dysarthria, dizziness,
confusion, hypesthesia, vertigo, incoordination, and parkinsonism have been
reported with the use of valproate. Rare cases of coma have occurred in
patients receiving valproate alone or in conjunction with phenobarbital. In
rare instances encephalopathy with or without fever has developed shortly after
the introduction of valproate monotherapy without evidence of hepatic
dysfunction or inappropriately high plasma valproate levels. Although recovery
has been described following drug withdrawal, there have been fatalities in patients
with hyperammonemic encephalopathy, particularly in patients with underlying
urea cycle disorders [see WARNINGS AND PRECAUTIONS].

Several reports have noted reversible cerebral atrophy
and dementia in association with valproate therapy.

Dermatologic

Transient hair loss, skin rash, photosensitivity,
generalized pruritus, erythema multiforme, and Stevens-Johnson syndrome. Rare
cases of toxic epidermal necrolysis have been reported including a fatal case
in a 6 month old infant taking valproate and several other concomitant
medications. An additional case of toxic epidermal necrosis resulting in death
was reported in a 35 year old patient with AIDS taking several concomitant
medications and with a history of multiple cutaneous drug reactions. Serious
skin reactions have been reported with concomitant administration of
lamotrigine and valproate [see DRUG INTERACTIONS].

Hepatic

Minor elevations of transaminases (e.g., SGOT and SGPT)
and LDH are frequent and appear to be dose-related. Occasionally, laboratory
test results include increases in serum bilirubin and abnormal changes in other
liver function tests. These results may reflect potentially serious
hepatotoxicity [see WARNINGS AND PRECAUTIONS].